1. Field of the Invention
The present invention relates to a novel carbapenem derivative and, more specifically, to a carbapenem derivative exhibiting an antimicrobial activity against various microorganisms, particularly against methicillin-resistant Staphylococcus aureus (MRSA) which has recently been identified as a cause of hospital acquired infection, and useful not only as a medicine for human beings but also in veterinary medicine. The present invention also relates to a pharmaceutical composition, particularly to an antimicrobial agent, comprising this carbapenem derivative as an effective component.
2. Description of the Background Art
A number of studies have been undertaken about carbapenem type antibiotics because of their possession of strong and broad antimicrobial activities. These studies have confirmed that the antimicrobial activities of carbapenem compounds largely differ according to three asymmetrical carbon atoms 1', 5, and 6 on the basic carbapenem molecular structure shown below, that is, a combination of the configuration for these three carbon atoms, and also to the kind of substituent on the position 2 (for example, ".beta.-Lactam-based medicines" (Nankodo, 1987), pp 664-685, coedited by UEDA and SHIMIZU). ##STR2##
The carbapenem compounds with the configuration (1'R,5R,6S) is known to exhibit the strongest activity (e.g., ".beta.-Lactam-based medicines" (Nankodo, 1987), pp 664-685, coedited by UEDA and SHIMIZU). Most carbapenem compounds currently known have this configuration.
Several naturally occurring carbapenem compounds with the configuration (1'S,5R,6R) are also known in the art (e.g., Chemistry and Biology of .beta.-lactam Antibiotics, Vol. 2 (1982), pp 227-251, Eds. R. B. Morin and M. Gorman, Academic Press, New York). The activity of these naturally occurring carbapenem compounds is not so strong as that of the carbapenem compounds with the configuration (1'R,5R,6S).
Therefore, only replacement of the substituent on the position 2 has been considered to be effective for improving the activity of carbapenem compounds.
Ineffectiveness of almost all conventional antibiotics against high resistant MRSA (methicillin-resistant Staphylococcus aureus), the incidence of which is expected to increase, is a big issue. Development of antibiotics which are effective against both the MRSA and other many conventionally known bacteria has been strongly desired.
The present inventors have undertaken extensive studies paying attention to carbapenem compounds to discover a compound possessing a powerful antimicrobial activity against a wide variety of microorganisms. The present inventors have synthesized a great number of carbapenem derivatives, while paying attention particularly to the configuration of the 6 position substituent, the configuration on the .beta.-lactam ring, and the 2 position substituent of carbapenem compounds, and have examined the antimicrobial activities of the synthesized carbapenem derivatives and conventionally known carbapenem derivatives.
As a result, the present inventors have found that carbapenem derivatives possessing specific substituents and specific configurations exhibit strong antimicrobial activity against a wide variety of microorganisms, particularly against MRSA. This finding has led to the completion of the present invention.